A Bioequivalence Study of Darunavir, Emtricitabine, and Tenofovir Alafenamide, in the Presence of Cobicistat in Healthy Participants

NCT02578550 | Completed Phase 1

• 3 other identifiers: CR107887TMC114FD2HTX10012015-001264-18
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the single-dose pharmacokinetics and pivotal bioequivalence of Darunavir (DRV) 800 milligram (mg), Emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg when administered as a fixed-dose combination (FDC) (D/C/F/TAF) relative to the separate agents (DRV 800 mg tablet formulation and FTC/TAF 200/10 mg FDC) in the presence of 150 mg Cobicistat (COBI), under fed conditions, in healthy participants.

Conditions

Healthy

Keywords

Immunodeficiency Virus Type 1, Human; Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide; Healthy participants

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide

  The Cmax is the maximum observed plasma concentration.

  Up to 72 hours post-dose

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide

  The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

  Up to 72 hours post-dose

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Darunavir, Cobicistat, Emtricitabine and Tenofovir Alafenamide

  The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

  Up to 72 hours post-dose

Secondary Outcomes (9)

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)

  Up to 72 hours post-dose

• Plasma Concentration at the Last Quantifiable Time Point (Clast) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)

  Up to 72 hours post-dose

• Elimination Rate Constant (Lambda[z]) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)

  Up to 72 hours post-dose

• Elimination HalfLife (t1/2) of Darunavir (DRV), Cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)

  Up to 72 hours post-dose

• Time to Last Quantifiable Plasma Concentration (Tlast) of Darunavir (DRV), cobicistat (COBI), Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)

  Up to 72 hours post-dose

Study Arms (2)

Treatment Sequence (AB)

EXPERIMENTAL

Participant will receive a single oral tablet of darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination \[FDC\]) (Treatment A) in period 1, then 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 2

Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC); Drug: Emtricitabine/tenofovir alafenamide FDC; Drug: Darunavir; Drug: Cobicistat

Treatment Sequence (BA)

EXPERIMENTAL

Participant will receive 1 tablet of DRV 800 mg + 1 tablet of COBI 150 mg + 1 tablet of FTC/TAF 200/10 mg FDC (Treatment B) in period 1, then a single oral tablet of D/C/F/TAF (800/150/200/10 mg) FDC (Treatment A) in period 2

Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC); Drug: Emtricitabine/tenofovir alafenamide FDC; Drug: Darunavir; Drug: Cobicistat

Interventions

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide fixed-dose combination (FDC) DRUG

A single tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF 10 mg will be administered.

Treatment Sequence (AB); Treatment Sequence (BA)

Emtricitabine/tenofovir alafenamide FDC DRUG

A single tablet containing FTC 200 mg and TAF 10 mg will be administered.

Treatment Sequence (AB); Treatment Sequence (BA)

Darunavir DRUG

A single tablet containing darunavir 800 mg will be administered.

Treatment Sequence (AB); Treatment Sequence (BA)

Cobicistat DRUG

A single table containing cobistat 150 mg will be administered.

Treatment Sequence (AB); Treatment Sequence (BA)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be non-smoker for at least 3 months prior to selection

You may not qualify if:

• Participant must have a body mass index (BMI), between 18.5 and 30 kilogram per square meter (kg/m\^2) (inclusive)
• All female participants, except when postmenopausal, must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) pregnancy test at Screening and must not breastfeed from Screening onwards
• Participant has a positive human immunodeficiency virus - type (HIV-1) or human immunodeficiency virus - type 2 (HIV-2) test at Screening
• Participant has hepatitis A, B, or C infection (confirmed by a positive hepatitis A antibody immunoglobulin M (IgM), hepatitis B surface antigen, and/or hepatitis C virus antibody, respectively) at Screening
• Participant has currently significant and active gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, endocrinologic, genitourinary, renal, hepatic, respiratory, inflammatory, neoplastic, or infectious disease. Currently active dermatological disease that would interfere with a correct assessment of possible skin reactions to the study drugs
• Participant has currently significant and active diarrhea, nausea, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability
• Participant has any history of renal insufficiency

Sponsors & Collaborators

• Janssen Sciences Ireland UC: lead

Study Sites (1)

Unknown Facility

Groningen, Netherlands

Location

Related Publications (1)

• Crauwels HM, Baugh B, Van Landuyt E, Vanveggel S, Hijzen A, Opsomer M. Bioequivalence of the Once-Daily Single-Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability. Clin Pharmacol Drug Dev. 2019 May;8(4):480-491. doi: 10.1002/cpdd.628. Epub 2018 Nov 9.

  PMID: 30412360 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Darunavir; Cobicistat; emtricitabine tenofovir alafenamide; Emtricitabine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Janssen Sciences Ireland UC Clinical Trial

  Janssen Sciences Ireland UC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2015
• First Posted: October 19, 2015
• Study Start: November 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

NL (1)